Background

In the cuprizone murine model of demyelination neurotoxin cuprizone is fed to mice, inducing death of oligodendrocytes and consequent central nervous system (CNS) demyelination, which leads to demyelination-associated behavioral impairments, occurring within 5-7 weeks, with spontaneous remyelination after 4 weeks of diet suspension. In vitro experiments have demonstrated that neuronal electrical activity, which can be modulated in vivo through transcranial direct current stimulation (tDCS), is able to promote axonal remyelination. Moreover, anodal tDCS ameliorated motor and cognitive impairments in several experimental models of neurological disorders, including stroke, Parkinson’s disease and Alzheimer’s disease.

Objectives

To explore the usefulness of tDCS to promote recovery of demyelination-associated behavioral impairments during the remyelinization phase.

Methods

Male wild-type C57BL/6 (n = 31) were fed cuprizone (n = 19) or control regular diet (n = 12) for 7 weeks, followed by regular diet for one more week. At cuprizone suspension, anodal (n = 10) or sham (n = 9) tDCS (350 microA, 20 min) was performed under sevoflurane anesthesia through epicranial electrodes for 5 consecutive days. Motor performance was assessed through rotarod and spatial working memory through spontaneous alternation T-maze on the last two days of cuprizone diet and on the two days after the last tDCS treatment.

Results

At the end of cuprizone diet, a significant worsening of rotarod motor performance was observed in cuprizone mice vs controls (p = 0.0005). No significant effects were found on T-maze. After neurostimulation, anodal tDCS led to a significant rescue of motor performance in cuprizone mice (post-tDCS vs pre-tDCS: p < 0.0001). After tDCS, motor performance of anodal-stimulated mice was significantly higher than the one of sham-stimulated mice (p = 0.004). While sham-stimulated mice were significantly impaired in comparison with healthy control mice (p = 0.030), anodal-stimulated mice were comparable to healthy mice (p = 0.326). Anodal, but not sham, tDCS rescued motor impairment of cuprizone mice (healthy: 231.8 sec; sham: 138 sec; anodal: 271.6 sec).

Conclusions

These findings reveal a promising role of anodal tDCS in promoting remyelination in the cuprizone model and prompt further experiments exploring the potential of this technique. Indeed, tDCS could represent an innovative, non invasive and easy to use remyelination-boosting treatment.

Supported by: Fondazione Italiana Sclerosi Multipla (FISM 2018/B/3).